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Diet-Induced Abdominal Obesity, Metabolic Changes, and Atherosclerosis in Hypercholesterolemic Minipigs.

ABSTRACT: Background:Obesity and metabolic syndrome (MetS) are major risk factors for atherosclerotic diseases; however, a causal link remains elusive. Animal models resembling human MetS and its complications, while important, are scarce. We aimed at developing a porcine model of human MetS. Methods:Forty pigs with familial hypercholesterolemia were fed a high fat?+?fructose diet for 30 weeks. Metabolic assessments and subcutaneous fat biopsies were obtained at 18 and 30 weeks, and fat distribution was assessed by CT-scans. Postmortem, macrophage density, and phenotype in fat tissues were quantified along with atherosclerotic burden. Results:During the experiment, we observed a >4-fold in body weight, a significant but small increase in fasting glucose (4.1?mmol/L), insulin (3.1?mU/L), triglycerides (0.5?mmol/L), and HDL cholesterol (2.6?mmol/L). Subcutaneous fat correlated with insulin resistance, but intra-abdominal fat correlated inversely with insulin resistance and LDL cholesterol. More inflammatory macrophages were found in visceral versus subcutaneous fat, and inflammation decreased in subcutaneous fat over time. Conclusions:MetS based on human criteria was not achieved. Surprisingly, visceral fat seemed part of a healthier metabolic and inflammatory profile. These results differ from human findings, and further research is needed to understand the relationship between obesity and MetS in porcine models.

SUBMITTER: Al-Mashhadi AL

PROVIDER: S-EPMC5845503 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Diet-Induced Abdominal Obesity, Metabolic Changes, and Atherosclerosis in Hypercholesterolemic Minipigs.

Al-Mashhadi Ahmed Ludvigsen AL Poulsen Christian Bo CB von Wachenfeldt Karin K Robertson Anna-Karin AK Bentzon Jacob Fog JF Nielsen Lars Bo LB Thygesen Jesper J Tolbod Lars Poulsen LP Larsen Jens Rolighed JR Moestrup Søren Kragh SK Frendéus Björn B Mortensen Brynjulf B Drouet Ludovic L Al-Mashhadi Rozh H RH Falk Erling E

Journal of diabetes research 20180225

<h4>Background</h4>Obesity and metabolic syndrome (MetS) are major risk factors for atherosclerotic diseases; however, a causal link remains elusive. Animal models resembling human MetS and its complications, while important, are scarce. We aimed at developing a porcine model of human MetS.<h4>Methods</h4>Forty pigs with familial hypercholesterolemia were fed a high fat + fructose diet for 30 weeks. Metabolic assessments and subcutaneous fat biopsies were obtained at 18 and 30 weeks, and fat dis ...[more]

PMID: 29682581

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Project description:ObjectiveObesity and osteoarthritis (OA) are 2 major public health issues affecting millions of people worldwide. Whereas parental obesity affects the predisposition to diseases such as cancer or diabetes in children, transgenerational influences on musculoskeletal conditions such as OA are poorly understood. This study was undertaken to assess the intergenerational effects of a parental/grandparental high-fat diet on the metabolic and skeletal phenotype, systemic inflammation, and predisposition to OA in 2 generations of offspring in mice.MethodsMetabolic phenotype and predisposition to OA were investigated in the first and second (F1 and F2) generations of offspring (n = 10-16 mice per sex per diet) bred from mice fed a high-fat diet (HFD) or a low-fat control diet. OA was induced by destabilizing the medial meniscus. OA, synovitis, and adipose tissue inflammation were determined histologically, while bone changes were measured using micro-computed tomography. Serum and synovial cytokines were measured by multiplex assay.ResultsParental high-fat feeding showed an intergenerational effect, with inheritance of increased weight gain (up to 19% in the F1 generation and 9% in F2), metabolic imbalance, and injury-induced OA in at least 2 generations of mice, despite the fact that the offspring were fed the low-fat diet. Strikingly, both F1 and F2 female mice showed an increased predisposition to injury-induced OA (48% higher predisposition in F1 and 19% in F2 female mice fed the HFD) and developed bone microarchitectural changes that were attributable to parental and grandparental high-fat feeding.ConclusionThe results of this study reveal a detrimental effect of parental HFD and obesity on the musculoskeletal integrity of 2 generations of offspring, indicating the importance of further investigation of these effects. An improved understanding of the mechanisms involved in the transmissibility of diet-induced changes through multiple generations may help in the development of future therapies that would target the effects of obesity on OA and related conditions.

Dataset Information

Diet-Induced Abdominal Obesity, Metabolic Changes, and Atherosclerosis in Hypercholesterolemic Minipigs.

Publications

Diet-Induced Abdominal Obesity, Metabolic Changes, and Atherosclerosis in Hypercholesterolemic Minipigs.

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